Biocompatible Material

ABSTRACT

A biocompatible material having excellent biocompatibility such as small interaction with a component of a living body such as a protein or blood cell. A biocompatible material comprising a polymer obtained by polymerizing a monomer composition comprising an amino acid-type betaine monomer represented by the formula (I): 
     
       
         
         
             
             
         
       
     
     wherein R 1  is a hydrogen atom or a methyl group; R 2  is an alkylene group having 1 to 6 carbon atoms; each of R 3  and R 4  is independently an alkyl group having 1 to 4 carbon atoms; R 5  is an alkylene group having 1 to 4 carbon atoms; and Z is an oxygen atom or an —NH group; and a polymerizable monomer represented by the formula (II): 
     
       
         
         
             
             
         
       
     
     wherein R 1  is as defined above; and R 6  is a monovalent organic group, in a weight ratio, i.e. amino acid-type betaine monomer/polymerizable monomer, of from 1/99 to 100/1. The biocompatible material can be suitably used, for example, in food, a food additive, a medicament, a quasi-drug, a medical device, cosmetics, a toiletry article, or the like.

TECHNICAL FIELD

The present invention relates to a biocompatible material. Morespecifically, the present invention relates to a biocompatible materialwhich can be suitably used in food, a food additive, a medicament, aquasi-drug, a medical device, cosmetics, a toiletry article, or thelike.

BACKGROUND ART

Biocompatible materials have been expected to be applied in variousfields. Presently, artificial materials such as silicone, polyethylene,and polyurethane have been used in medical devices such as medical tubesand catheters. However, these materials are recognized as a foreignsubstance by a living body, so that there are some risks that thematerials are denatured by adsorbing a protein or blood cells tosurfaces thereof, and that the materials themselves are activated tocause rejection such as coagulation of blood.

On the other hand, as a material having a glycine-type betaine monomeras a side chain, a glycine-type betaine resin in which betaine is formedby treating with sodium chloroacetate or the like, a polymer obtained byhomopolymerizing N,N-dimethylaminoethyl methacrylate, or copolymerizingN,N-dimethylaminoethyl methacrylate with another monomer, or the likehas been known (see, for example, Patent Publications 1 to 3).

However, there are some disadvantages in these betaine resins that sinceit is difficult to perfectly terminate a betaine formation reaction, anN,N-dimethylamino group would remain in the resin, and the remainingN,N-dimethylamino group gives disadvantageous influence tobiocompatibility.

Patent Publication 1: Japanese Patent Laid-Open No. Sho 51-9732

Patent Publication 2: Japanese Patent Laid-Open No. Sho 55-104209

Patent Publication 3: Japanese Patent Laid-Open No. Sho 56-92809

DISCLOSURE OF INVENTION Problems to be Solved by the Invention

The present invention has been accomplished in view of theabove-mentioned prior art, and an object of the present invention is toprovide a biocompatible material having excellent biocompatibility suchas small interaction with a component of a living body such as a proteinor blood cell for the development of advanced medical devices orartificial organs of the next generation.

Means to Solve the Problems

The present invention relates to a biocompatible material comprising apolymer obtained by polymerizing a monomer composition comprising anamino acid-type betaine monomer represented by the formula (I):

wherein R¹ is a hydrogen atom or a methyl group; R² is an alkylene grouphaving 1 to 6 carbon atoms; each of R³ and R⁴ is independently an alkylgroup having 1 to 4 carbon atoms; R⁵ is an alkylene group having 1 to 4carbon atoms; and Z is an oxygen atom or an —NH group; and apolymerizable monomer represented by the formula (II):

wherein R¹ is as defined above; and R⁶ is a monovalent organic group,

in a weight ratio, i.e. amino acid-type betaine monomer/polymerizablemonomer, of from 1/99 to 100/1.

EFFECTS OF THE INVENTION

The biocompatible material of the present invention has excellentbiocompatibility such as little interaction with a component of a livingbody such as a protein or blood cell for the development of advancedmedical devices or artificial organs of the next generation. Since thebetaine monomer represented by the formula (I) is used in thebiocompatible material of the present invention, there is an advantagethat molecular design can be freely carried out depending upon itsapplications.

BRIEF DESCRIPTION OF THE DRAWINGS

[FIG. 1] A graph showing the results of evaluation of non-specificadsorption of bovine serum albumin (dΔEp) in Experimental Example 1.

[FIG. 2] A graph showing the results of evaluation of non-specificadsorption of bovine serum albumin (ΔI) in Experimental Example 1.

[FIG. 3] A graph showing the results of evaluation of non-specificadsorption of lysozyme (dΔEp) in Experimental Example 1.

BEST MODE FOR CARRYING OUT THE INVENTION

In a betaine monomer represented by the formula (I), R¹ is a hydrogenatom or a methyl group. R² is an alkylene group having 1 to 6 carbonatoms. Each of R³ and R⁴ is independently an alkyl group having 1 to 4carbon atoms. R⁵ is an alkylene group having 1 to 4 carbon atoms. Z isan oxygen atom or an —NH group.

Specific examples of the betaine monomer represented by the formula (I)includeN-(meth)acryloyloxymethyl-N,N-dimethylammonium-α-N-methylcarboxybetaine,N-(meth)acryloyloxyethyl-N,N-dimethylammonium-α-N-methylcarboxybetaine,N-(meth)acryloyloxypropyl-N,N-dimethylammonium-α-N-methylcarboxybetaine,N-(meth)acryloyloxymethyl-N,N-diethylammonium-α-N-methylcarboxybetaine,N-(meth)acryloyloxyethyl-N,N-diethylammonium-α-N-methylcarboxybetaine,N-(meth)acryloyloxypropyl-N,N-diethylammonium-α-N-methylcarboxybetaine,and the like. These monomers can be used alone or in admixture of two ormore kinds.

The term “(meth)acry-” as used herein refers to “acry-” or “methacry-.”

Among the betaine monomers represented by the formula (I),N-methacryloyloxyethyl-N,N-dimethylammonium-α-N-methylcarboxybetainerepresented by the formula (III):

is preferable. The betaine monomer represented by the formula (I) asrepresented byN-methacryloyloxyethyl-N,N-dimethylammonium-α-N-methylcarboxybetaine iseasily available in high purity by a method described, for example, inJP-A-Hei-9-95474, JP-A-Hei-9-95586, JP-A-Hei-11-222470, or the like.

In a polymerizable monomer represented by the formula (II), R¹ is asdefined above. R⁶ is a monovalent organic group. Representative examplesof R⁶ include a —COOR⁷ group (R⁷ is an alkyl group having 1 to 22 carbonatoms), a —COO—R⁸—OH group (R⁸ is an alkenyl group having 1 to 4 carbonatoms), a —CONR⁹R¹⁰ group (each of R⁹ and R¹⁰ is independently ahydrogen atom, an alkyl group having 1 to 4 carbon atoms), a —OCO—R¹¹group (R¹¹ is a methyl group or an ethyl group), a group represented bythe formula (IV):

wherein R¹² is an alkylene group having 3 or 5 carbon atoms, a grouprepresented by the formula (V):

wherein R¹³ is an alkyl group having 2 to 9 carbon atoms, and R¹⁴ is ahydrogen atom or a methyl group,

and the like. Among the above-mentioned R⁶, the —COO—R⁸—OH group, the—COOR⁷ group, the —CONR⁹R¹⁰ group, and the group represented by theformula (IV) are preferable from the viewpoint of biocompatibility.

Specific examples of the polymerizable monomer represented by theformula (II) include monofunctional monomers such as methyl(meth)acrylate, ethyl (meth)acrylate, n-butyl (meth)acrylate, isobutyl(meth)acrylate, t-butyl (meth)acrylate, neopentyl (meth)acrylate,cyclohexyl (meth)acrylate, benzyl (meth)acrylate, octyl (meth)acrylate,lauryl (meth)acrylate, stearyl (meth)acrylate, cetyl (meth)acrylate,ethyl carbitol (meth)acrylate, hydroxyethyl (meth)acrylate,hydroxypropyl (meth)acrylate, hydroxybutyl (meth)acrylate, methoxyethyl(meth)acrylate, methoxybutyl (meth)acrylate, N-methyl (meth)acrylamide,N-ethyl (meth)acrylamide, N-propyl (meth)acrylamide, N-isopropyl(meth)acrylamide, N-butoxymethyl (meth)acrylamide, N-t-butyl(meth)acrylamide, N-octyl (meth)acrylamide, N,N-dimethyl(meth)acrylamide, N,N-diethyl (meth)acrylamide, (meth)acryloylmorpholine, diacetone (meth)acrylamide, styrene, methyl itaconate, ethylitaconate, vinyl acetate, vinyl propionate, N-vinyl pyrrolidone, andN-vinyl caprolactam; polyfunctional monomers such as 1,4-butanedioldi(meth)acrylate, 1,6-hexanediol di(meth)acrylate, 1,9-nonanedioldi(meth)acrylate, 2-n-butyl-2-ethyl-1,3-propanediol di(meth)acrylate,tripropyleneglycol di(meth)acrylate, tetraethyleneglycoldi(meth)acrylate, methylenebisacrylamide, trimethylolpropanetri(meth)acrylate, and pentaerythritol tri(meth)acrylate; and the like.These monomers can be used alone or in admixture of two or more kinds.

Among the polymerizable monomers represented by the formula (II), butyl(meth)acrylate, stearyl (meth)acrylate, N,N-dimethyl acrylamide, N-vinylpyrrolidone, hydroxyethyl (meth)acrylate, and the like are preferablefrom the viewpoint of biocompatibility.

Amounts of the betaine monomer represented by the formula (I) and thepolymerizable monomer represented by the formula (II) cannot beunconditionally determined because the amounts would differ dependingupon the region of body where a biocompatible material is used, purposeof use, or the like. The amounts of the both monomers are adjusted sothat the betaine monomer represented by the formula (I)/thepolymerizable monomer represented by the formula (II), in a weightratio, is from 1/99 to 100/0, preferably from 5/95 to 95/5, and morepreferably from 10/90 to 90/10, from the viewpoint of biocompatibility,hydrophilicity, water resistance, adsorbability of a biologicalcomponent, rigidity, workability, or the like.

Here, when a monomer composition is composed only of a betaine monomerrepresented by the formula (I), the resulting polymer is a homopolymerof the betaine monomer represented by the formula (I). When a monomercomposition is composed of a betaine monomer represented by the formula(I) and a polymerizable monomer represented by the formula (II), theresulting polymer is a copolymer of the betaine monomer represented bythe formula (I) and the polymerizable monomer represented by the formula(II).

A polymer constituting a biocompatible material can be prepared bypolymerizing a monomer composition, for example, by a solutionpolymerization using water or an organic solvent as a solvent. Morespecifically, the polymer can be obtained by dissolving a monomercomposition containing given amounts of a betaine monomer represented bythe formula (I) and a polymerizable monomer represented by the formula(II) in purified water or an organic solvent; adding a polymerizationinitiator to the resulting solution while stirring; and polymerizing themonomer composition in an inert gas atmosphere.

The organic solvent includes, for example, alcohols such as methylalcohol, ethyl alcohol, isopropyl alcohol, ethylene glycol, andpropylene glycol; ketones such as acetone and methyl ethyl ketone; alkylethers such as diethyl ether and tetrahydrofuran; aromatic compoundssuch as benzene, toluene, and xylene; aliphatic hydrocarbon compoundssuch as n-hexane; alicyclic hydrocarbon compounds such as cyclohexane,acetic acid esters such as methyl acetate and ethyl acetate; and thelike. The present invention is not limited to those exemplified above.

It is preferable that the concentration of the monomer composition inthe solution of the monomer composition usable in the solutionpolymerization is from 10 to 80% by weight or so, in consideration ofoperability of polymerization, or the like.

During the polymerization, it is preferable to use a polymerizationinitiator. The polymerization initiator is not particularly limited, andincludes, for example, ordinary azo-based polymerization initiators andperoxide-based polymerization initiators, such as azoisobutyronitrile,methyl azoisobutyrate, azobisdimethylvaleronitrile, benzoyl peroxide,potassium persulfate, and ammonium persulfate; and photopolymerizationinitiators such as benzophenone derivatives, phosphine oxidederivatives, benzoketone derivatives, phenylthio ether derivatives,azide derivatives, diazo derivatives, and disulfide derivatives; and thelike. It is preferable that the amount of the polymerization initiatoris usually from 0.01 to 5 parts by weight or so, based on 100 parts byweight of the monomer composition.

During the polymerization, a chain transfer agent can be optionallyused. The chain transfer agent includes, compounds having a mercaptangroup such as laurylmercaptan, dodecylmercaptan, and thioglycerol;inorganic salts such as sodium hypophosphite and sodium hydrogensulfite;and the like, and the present invention is not intended to be limitedonly to those exemplified. It is preferable that the amount of the chaintransfer agent is usually from 0.01 to 10 parts by weight or so, basedon 100 parts by weight of the monomer composition.

The polymerization temperature of the monomer composition cannot beunconditionally determined, because the polymerization temperaturevaries depending upon the kinds of the polymerization initiator used.Usually, it is preferable that the polymerization temperature is a10-hour half-life temperature of the polymerization initiator. It isdesired that the polymerization time is 2 hours or more, preferably from2 to 24 hours or so, from the viewpoint avoiding unreacted monomers tobe remaining in the reaction mixture. The polymerization of the monomercomposition can be carried out in an atmosphere of an inert gas. Theinert gas includes, for example, nitrogen gas, argon gas, and the like.

The presence or absence of the unreacted monomer in the reaction systemcan be confirmed by a general analyzing method such as gaschromatography.

Thus, a polymer can be obtained by polymerizing a monomer composition.The resulting polymer can be collected by fractionating the reactionmixture using an ultrafiltration membrane or the like, and optionallycleaning according to an ordinary method.

The resulting polymer has a weight-average molecular weight ofpreferably from 500 to 2,000,000, more preferably from 1,000 to1,000,000, from the viewpoint of handling ability during production, andworkability of the formed product.

The biocompatible material of the present invention comprises theabove-mentioned polymer. The biocompatible material of the presentinvention may be constituted by the above-mentioned polymer alone, ormay be optionally constituted by the above-mentioned polymer and otherpolymer within the range that would not impede the object of the presentinvention.

Since the biocompatible material of the present invention has excellentbiocompatibility, the biocompatible material can be suitably used infood, a food additive, a medicament, a quasi-drug, a medical device,cosmetics, a toiletry article, or the like.

The food and the food additive include, for example, those that are usedin ordinary foods, such as thickening agents, pH adjustment agents,molding aids, and wrapping materials; the medicament, the quasi-drug,and the medical device include, for example, drug delivery systemagents, artificial blood vessels, blood dialysis membranes, catheters,contact lenses, blood filters, blood storage bags, artificial organs,and the like; the cosmetics and the toiletry article include, forexample, shampoos, rinses, conditioners, milky lotions, moisturizingcream, soaps, skin cleaning agents, pack agents, cortical peelingagents, hair-styling agents, hair-dyes, hair decolorizing agents,permanent agents, perfumes, antiperspirants, refreshing agents,disposable diapers, sanitary articles, bath detergents, dishwashingdetergents, filtration filters for tap water, and the like, and thepresent invention is not limited only to those exemplified.

EXAMPLES

The present invention will be specifically described hereinbelow by theExamples, without intending to limit the scope of the present inventionthereto.

Example 1

The amount 11.9 mg of tetraethylthiuram disulfide was added as aphotopolymerization initiator to a monomer composition composed of 234mg ofN-methacryloyloxyethyl-N,N-dimethylammonium-α-N-methylcarboxybetaine and13.6 mg of bis[4-(N,N-diethyldithiocarbamoylmethyl)benzylamide ethylsulfide]. Thereafter, the mixture was dissolved in a mixed solvent of2.5 mL of methanol and 1 mL of tetrahydrofuran, and nitrogen gas wasallowed to pass through the resulting solution for 15 minutes.Subsequently, the solution was irradiated with ultraviolet rays at atemperature of 25° C. in an nitrogen gas atmosphere for 4 hours, tosubject the monomer composition to photopolymerization.

Next, the polymerized mixture was fractionated by ultrafiltration(fractionated molecular weights: 3,000 to 10,000), and the fraction waslyophilized to collect the formed polymer (yield: 45 mg). Degree ofpolymerization and weight-average molecular weight of the resultingpolymer were examined by H¹—NMR. As a result, the degree ofpolymerization was 23.1, and the weight-average molecular weight was5,500. The determination results for H¹—NMR are as follows.

¹H-NMR (400 MHz, D₂O): 1.08 (t, m, 3H, 2H, —CH₃, —CH₂—),

2.21 (m, 2H, —CH₂—), 3.38 (t, 2H, 3H, N—CH₂—, N—CH₃),

3.70 (m, 2H, 2H, N—CH₂—, —CH₂—COOH), 4.76 (d, 2H, O—CH₂—),

7.2-7.8 (m, 4H, -Ph-)

Example 2

The same procedures as in Example 1 were carried out except for using250 mg of a mixture of butyl methacrylate andN-methacryloyloxyethyl-N,N-dimethylammonium-α-N-methylcarboxybetaine[weight ratio of butylmethacrylate/N-methacryloyloxyethyl-N,N-dimethylammonium-α-N-methylcarboxybetaine:4/6] as a monomer composition in Example 1, to give a polymer.

Next, the polymerized mixture was fractionated by ultrafiltration(fractionated molecular weights: 3,000 to 10,000), and the fraction waslyophilized to collect the formed polymer (yield: 50 mg). Weight-averagemolecular weight of the resulting polymer was examined by H¹—NMR. As aresult, the weight-average molecular weight was 18,000.

Example 3

Twenty-five milliliters of methanol was added to 5.0 g ofN-methacryloyloxyethyl-N,N-dimethylammonium-α-N-methylcarboxybetaine,and 70.8 mg of 2,2-azobisisobutyronitrile as a polymerization initiatorand 0.15 mL of 2-mercaptoethanol as a chain transfer agent were addedthereto, and the components were polymerized at 70° C. for 24 hours.Thereafter, the polymerized mixture was concentrated, and theconcentrate was further dissolved in water. The solution wasfractionated by dialysis (fractionated molecular weight: 1,000), and thefraction was lyophilized to collect the formed polymer (yield: 3.6 g).Weight-average molecular weight of the resulting polymer was examined bygel permeation chromatography (mobile phase: a 0.1 M aqueous sodiumbromide containing 0.5% lithium bromide). As a result, theweight-average molecular weight was 11,400.

Example 4

The amount 2.23 mL ofN-methacryloyloxyethyl-N,N-dimethylammonium-α-N-methylcarboxybetaine andbutyl methacrylate [weight ratio ofN-methacryloyloxyethyl-N,N-dimethylammonium-α-N-methylcarboxybetaine/butylmethacrylate: 45/55] was used in place of 5.0 g ofN-methacryloyloxyethyl-N,N-dimethylammonium-α-N-methylcarboxybetaine inExample 2, and the components were polymerized at 70° C. for 24 hours.Thereafter, the polymerized mixture was introduced into n-hexane toprecipitate the polymer, and the precipitates were further dissolved inwater. The solution was fractionated by dialysis (fractionated molecularweight: 3,500), and the fraction was lyophilized to collect the formedpolymer (yield: 1.6 g). Weight-average molecular weight of the resultingpolymer was examined by gel permeation chromatography (mobile phase: a0.1 M aqueous sodium bromide containing 0.5% lithium bromide). As aresult, the weight-average molecular weight was 17,800.

Comparative Example 1

The same procedures as in Example 1 were carried out except that 234 mgof methacrylic acid was used in place of 234 mg ofN-methacryloyloxyethyl-N,N-dimethylammonium-α-N-methylcarboxybetaine.Degree of polymerization and weight-average molecular weight of theresulting polymer were examined by H¹-NMR. As a result, the degree ofpolymerization was 16, and the weight-average molecular weight was2,700.

Comparative Example 2

For the sake of comparison with Example 2, sodium polyethylenesulfonate(weight-average molecular weight: 2,200) was used.

Comparative Example 3

For the sake of comparison with Example 2, poly-L-lysine hydrobromide(weight-average molecular weight: 2,700) was used.

Comparative Example 4

For the sake of comparison with Example 2, polyethylene glycol(weight-average molecular weight: 2,000) was used.

Comparative Example 5

For the sake of comparison with Example 2, poly-N-vinylpyrrolidone(weight-average molecular weight: 2,300) was used.

Experimental Example 1

Next, a self-organizing monomolecular film made of the polymer eachobtained in Example 1 and Comparative Example 1 was examined for itscyclic voltammetry.

More specifically, as an electrode, a gold electrode (AUE 6.0×1.6 mm;BAS) was polished with alumina powder, and thereafter this goldelectrode was irradiated with ultrasonic wave (Sine Sonic 150, Sine) for30 seconds. The procedures were repeated several times, and thereafterthe electrode was immersed in a 0.1 N aqueous sulfuric acid or a 0.5 Naqueous potassium hydroxide, and voltage was applied thereto, using acyclic voltammogram (POTENTIOSTAT: manufactured by Hokuto DenkoCorporation, product number: HA-301), a functional generator[manufactured by Hokuto Denko Corporation, product number: HA-104], apower supply, and a alternating current-direct current converter[manufactured by Epson, product number: PC-486 SE]. Here, when a 0.1 Naqueous sulfuric acid was used, a voltage of from −0.4 to 1.5 V wasapplied thereto, and when a 0.5 N aqueous potassium hydroxide was used,a voltage of from 0 to −1.5 V was applied thereto.

Next, the surface of the gold electrode was washed, and thereafter thegold electrode was immersed in an aqueous solution containing 0.5 Mpotassium chloride and 5 mM potassium hexacyanoferrate(III), and cyclicvoltammogram was examined at a sweep rate of 10 mV/s and a appliedvoltage of from 0.6 to −0.3 V. After having confirmed that a potentialdifference (hereinafter referred to as ΔEp) was 65 mV or less, this goldelectrode was used.

The above-mentioned gold electrode was immersed in a 1 mg/mL aqueoussolution of the material obtained in Example 1 and Comparative Example 1for 24 hours, and thereafter washed several times with purified water.

The gold electrode modified with the materials obtained in Example 1 andComparative Example 1 was observed for protein non-specific adsorptionusing a 10 mM phosphate buffer having a pH of 7.0, the phosphate buffercontaining 1 mM hydroquinone and 0.1 M sodium sulfate (hereinafterreferred to a HQ solution).

Bovine serum albumin (BSA, pI: 4.8, 66 kD) or lysozyme (pI: 10.9, 1.4kD) was dissolved in a 10 mM phosphate buffer having a pH of 7.0, togive a protein solution (1 mg/mL). Before immersion in the proteinsolution, the electrode was examined for the cyclic voltammogram withthe HQ solution, and its potential difference was defined as 0 mV.Thereafter, the electrode was immersed in the protein solution, liftedaway from the solution in a given time interval to be washed severaltimes with purified water, and examined for the cyclic voltammogram withthe HQ solution.

ΔEp before immersion of the electrode in protein was subtracted from ΔEpafter the immersion, and the resultant value was defined as dΔEp.

In a case where the protein or the like is not found to be adsorbed on asurface of the self-organizing monomolecular film, since no substancesbesides the adsorbate impede transfer of a reduction-oxidationsubstance, the value of dΔEp would be 0 mV. In addition, when theenvironment on the self-organizing monomolecular film undergoes a changecaused by non-specific adsorption or the like, the transfer of thereduction-oxidation substance is impeded, so that the value of dΔEpincreases. Utilizing the phenomena, the non-specific adsorption or thelike of the protein was observed. The results are shown in FIGS. 1 to 3.

FIG. 1 is a graph showing the results of evaluation of non-specificadsorption of bovine serum albumin (dΔEp) in Experimental Example 1. Itcan be seen from the results shown in FIG. 1 that the value of dΔEp ofExample 1 is nearly 0, hardly showing any changes, whereas cases wherethe value of dΔEp increases as in a case where a gold electrode withoutformation of a monomolecular film is used (Bare Au in FIG. 1) and a caseof Comparative Example 1. It can be seen from this finding that the goldelectrode in which a self-organizing monomolecular film made of abiocompatible material according to Example 1 is formed has a smallamount of protein adsorbed to its surface, so that the gold electrode isexcellent in biocompatibility.

FIG. 2 is a graph showing the results of evaluation of non-specificadsorption of bovine serum albumin (ΔI) in Experimental Example 1. Itcan be seen from the results shown in FIG. 2 that the value of ΔI ofExample 1 hardly shows any changes, whereas cases where the value of ΔIdramatically lowers as in a case where a gold electrode withoutformation of a monomolecular film is used (Bare Au in FIG. 2). It can beseen from this finding that the gold electrode in which aself-organizing monomolecular film made of a biocompatible materialaccording to Example 1 is formed has a small amount of protein adsorbedto its surface, so that the gold electrode is excellent inbiocompatibility.

FIG. 3 is a graph showing the results of evaluation of non-specificadsorption of lysozyme (dΔEp) in Experimental Example 1. It can be seenfrom the results shown in FIG. 3 that the value of dΔEp of Example 1 isnearly 0, hardly showing any changes, whereas cases where the value ofdΔEp increases as in a case where a gold electrode without formation ofa monomolecular film is used (Bare Au in FIG. 3) and a case ofComparative Example 1. It can be seen from this finding that the goldelectrode in which a self-organizing monomolecular film made of abiocompatible material according to Example 1 is formed has a smallamount of protein adsorbed to its surface, so that the gold electrode isexcellent in biocompatibility.

It can be seen from the above results that the biocompatible materialobtained in Example 1 hardly adsorbs a protein such as bovine serumalbumin or lysozyme, so that the biocompatible material is excellent inbiocompatibility.

Experimental Example 2

The O—H stretching vibrations of water for the materials obtained inExamples 3 and 4 and Comparative Examples 2 to 5 were determined inaccordance with Raman spectroscopy.

More specifically, the O—H stretching vibrations of water weredetermined using a 10% by weight aqueous solution of each of thematerials obtained in Examples 3 and 4 and Comparative Examples 2 to 5in accordance with Raman spectroscopy. The results are shown in Table 1.Here, the determination conditions for Raman spectroscopy, and thedetermination methods for the N value and the N_(corr) value in Table 1are as follows.

[Determination Conditions for Raman Spectroscopy]

Raman spectrometer, manufactured by JASCO Corporation (product no.:NR-1100)Light source: Ar⁺ laser

Wavelength: 488 nm

Quantity of light: 200 mWResolution: 5 cm⁻¹

[Determination Methods for N Value and N_(corr) Value]

A possibility of excluding O—H vibrations from a network of hydrogenbonding of water molecules caused by undesired position and orientationdue to interaction of the solvents is represented by Pd. Pd is obtainedby the formula:

Pd=Cw−Cx)÷Cw,

wherein Cw is an O—H vibration intensity inherent in water; Cx is an O—Hvibration intensity of a solution.

The N value is the number of defects of hydrogen bonds introduced into anetwork structure of the hydrogen bonding of water per one monomer unitof a polymer. The N value is obtained by the formula:

NValue=Pd/Fx,

wherein Fx is the number of monomers per one O—H.

The C value is a relative intensity of a collective O—H stretchingvibration. Since a C value to pure water (C_(W)) is smaller than a Cvalue to perfect ice (C_(ice)), the N value is corrected by this factor,to give N_(corr) value, which is a corrective value of the N value. TheN_(corr) value is obtained by the formula:

N _(corr)Value=(CW/C _(ice))×NValue.

In addition, the C value is obtained by the formula:

CValue=∫Ic(w)dw/∫I _(//)(w)dw,

wherein Ic is a corrective intensity, and I_(//) is a parallelintensity, and the formula:

Ic=I _(//) −I _(⊥)/ρ,

wherein I_(//) is as defined above, I_(⊥) is a vertical intensity, and ρis a degree of depolarization.

TABLE 1 Weight-Average Molecular Weight N Value N_(corr) Value Ex. No. 311,400 −0.27 −0.18 4 17,800 0.02 0.02 Comp. Ex. 2 2,200 7.5 5.1 3 2,7008.1 5.5 4 2,000 1.0 0.7 5 2,300 0.9 0.6

It can be seen from the results shown in Table 1 that the materialsobtained in Examples 3 and 4 have smaller N values and N_(corr) valuesthan those of Comparative Examples 2 to 5, so that the network structureof hydrogen bonding of water near the polymer is hardly broken, wherebyshowing excellent biocompatibility.

INDUSTRIAL APPLICABILITY

Since the biocompatible material of the present invention is excellentin biocompatibility, the biocompatible material can be suitably used,for example, in food, a food additive, a medicament, a quasi-drug, amedical device, cosmetics, a toiletry article, or the like.

1. A biocompatible material comprising a polymer obtained bypolymerizing a monomer composition comprising an amino acid-type betainemonomer represented by the formula (I):

wherein R¹ is a hydrogen atom or a methyl group; R² is an alkylene grouphaving 1 to 6 carbon atoms; each of R³ and R⁴ is independently an alkylgroup having 1 to 4 carbon atoms; R⁵ is an alkylene group having 1 to 4carbon atoms; and Z is an oxygen atom or an —NH group; and apolymerizable monomer represented by the formula (II):

wherein R¹ is as defined above; and R⁶ is a monovalent organic group, ina weight ratio, i.e. amino acid-type betaine monomer/polymerizablemonomer, of from 1/99 to 100/1.
 2. The biocompatible material accordingto claim 1, wherein the amino acid-type betaine monomer isN-methacryloyloxyethyl-N,N-dimethylammonium-α-N-methylcarboxybetainerepresented by the formula (III):